Efficient Synthesis of Tetrahydro-β-carbolin-1-one and Dihydroisoquinolin-1-one Derivatives as Versatile Intermediates

Abstract

An efficient one-pot procedure is described in which an isocyanate intermediate, generated from the corresponding carboxylic acid by a modified Curtius rearrangement, is captured by a tethered aromatic ring in the presence of BF 3 •OEt 2 to generate various lactams, including tetrahydro-b-carbolin-1-one and dihydroisoquinolin-1-one derivatives.

Total Syntheses of β-Carboline Alkaloids Manzamine C, Orthoscuticelline C, and Quassidine S

“…Our synthesis commenced from a Curtius rearrangement reaction of commercially available acid 7 with diphenylphosphoryl azide (DPPA), followed by a ring closure reaction mediated by Lewis acid boron trifluoride etherate (BF 3 •OEt 2 ) to afford lactam 8 on a gram scale. 21 Desaturation of 8 with 2,3dichloro-5,6-dicyano-p-benzoquinone (DDQ), followed by transformation of the lactam to triflate afforded compound 9. 22 A Suzuki cross-coupling reaction with vinyl pinacol boronate generated the natural product pavettine (4) in good yield.…”

“…We first prepared pavettine ( 4 ) by a slight modification of the literature procedures (Scheme ). Our synthesis commenced from a Curtius rearrangement reaction of commercially available acid 7 with diphenylphosphoryl azide (DPPA), followed by a ring closure reaction mediated by Lewis acid boron trifluoride etherate (BF 3 ·OEt 2 ) to afford lactam 8 on a gram scale . Desaturation of 8 with 2,3-dichloro-5,6-dicyano- p -benzoquinone (DDQ), followed by transformation of the lactam to triflate afforded compound 9 .…”